Exudative age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR), due to aberrant choroidal and retinal neovascularization respectively, are two of the leading major causes of blindness in the US. PEDF (Pigment Epithelium-Derived Factor) is a potent endogenous antiangiogenic/neurotrophic factor and is purported to be the key natural regulator of vascularity in the eye. In experimental disease models, PEDF blocks choroidal and retinal neovascularization. Based on these compelling data, we hypothesize that periocular administration of PEDF using a gene-expressed production system (AdPEDF.11) may treat blinding ocular neovascular diseases such as wet AMD. Pedocular administration, to the space outside the sclera of the eye, is a well-established low risk procedure. Delivery to the periocular space avoids the potential morbidity of intraocular administration. In this Phase I application, we will test the feasibility of periocular administration in preclinical studies. We propose: 1) To determine PEDF expression levels in the eye after periocular delivery and compare the results to that found with intraocular delivery; 2) To determine if repeat periocular administration will result in elevated PEDF levels and 3) To evaluate whether PEDF will be expressed in animals that have high circulating neutralizing antibodies to adenovectors following a periocular administration of AdPEDF.11. Based on the data generated in the Phase I study, we will determine the scientific and commercial feasibility of using periocular administration as a means to deliver PEDF to patients with wet AMD. Successful completion of the above objectives will then provide the basis for future PEDF clinical studies using periocular administration. The goal of the SBIR Phase II grant will be to optimize further the periocular delivery method of AdPEDF.11 in preparation for clinical testing. Periocular delivery could provide a feasible and safer method of delivery of agents to the eye for wet AMD and other ocular diseases than intraocular methods.